免疫學(xué)課件-抗感染免疫

Anti-InfectionImmunity

抗感染免疫OutlineMechanismofspecificimmunityandnon-specificimmunityAntibacterialimmunityAntiviralimmunity

Nonspecificimmunity

Specificimmunity

(Innateimmunity)(Acquiredimmunity)SpecificImmunityInnateImmunitySpecificImmunityInnateImmunity&AcquiredimmunityNon-specificimmunitySpecificimmunity

notantigenspecificHeritableImmediateresponse

Exposuredoesnotresultininductionofmemorycells

AntigenspecificNon-heritableAlagtimebetweenexposureandmaximalresponse

ExposureresultininductionofmemorycellsNonspecificImmunityBarrierstructureMacrophageSkinandmucosaBarrier(antibacterialeffectsofnormalflora)BloodBrainBarrierPlacentalBarrier

NeutrophilMononuclearphagocytesystemAnti-bacterialsubstanceinserumandbodyfluidComplementsCytokinesLysozymeInterferonNaturalKillerCellSpecificImmunityHumoralImmunityCellImmunityMucosalimmunesystem(MIS)

Mechanismofanti-infectionimmunityUseothermicrobesasguard-dogsthatkillintruders

Thesearelistedfirstbecausetheyareontheoutsideofthebody,andthusformthefirstlineofdefense.MicrobesPhagocytosis?phagocytes*neutrophil*mononuclearphagocytesystem?processandmechanism?outcome*completephagocytosis*incompletephagocytosis*tissuedamageNeutrophilMonocyteMarcrophages中性粒細(xì)胞吞噬腦膜炎奈瑟菌StepOne:ChemotaxiscapillarybloodvesselphagocyteendotheliumbasementmembranePAVEMENTINGDIAPEDESISCHEMOTAXISC5aSiteofinflammation,tissuedamageandimmunereactionsC567C3aStepTwo:ContactStepThree:Phagocytosis/PinocytosisStepFour:Digest&DissolutionOxygenDependentROI&RNIMyeloperoxidase,MPOOxygenIndependentAcidLysosomeandotherenzymesNK細(xì)胞

自然殺傷細(xì)胞，存在于外周血和脾臟中，因含嗜天青顆粒，又稱大顆粒淋巴細(xì)胞。顆粒內(nèi)主要含穿孔素和顆粒酶主要通過(guò)ADCC作用殺傷靶細(xì)胞

*releasekillermediator

perforin(穿孔素)→necrosis

granzyme(顆粒酶)→apoptosis

TNF→necrosis/apoptosis

*mediateADCC?Recognitionandactivation?Killtargetcells(1)non-specific,Abindependent,non-MHCrestriction(2)MechanismofkillingtargetcellTcell分布：粘膜和上皮組織〔外周血含量少〕CD4-CD8-抗原識(shí)別譜：－－位于不同組織中的T細(xì)胞表達(dá)不同特異性的TCR，具有不同的抗原識(shí)別特性；－－同一部位組織的T具有相同的抗原識(shí)別特性，僅對(duì)同一抗原產(chǎn)生應(yīng)答多聚C9形成的膜攻擊復(fù)合物MAC的電鏡結(jié)果補(bǔ)體誘導(dǎo)的細(xì)胞膜穿孔損傷

GGGG

ooooMMMM

obobobob

GGGG

oooo

MMMMobobobob

GGGGooooMMMMaaaaccccddddaaaaccccddddxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxN-乙酰葡萄糖胺β-1,4糖苷鍵N-乙酰胞壁酸四肽側(cè)鏈

甘氨酸五肽(五肽交聯(lián)橋)金黃色葡萄球菌細(xì)胞壁肽聚糖結(jié)構(gòu)示意圖溶菌酶作用點(diǎn)聚糖骨架

PrincipalleukocytesfibroblastslymphocytescellsourceNKcellIFNinducersdsRNAdsRNAmitogensvirusvirusorantigenAntiviralinfection

+++++Anti-tumor++++Immunoregulation++++

PropertyIFN-

IFN-

IFN-

Interferon

(IFN)⑴

definition

干擾素是由病毒或其他干擾素誘生劑刺激機(jī)體多種細(xì)胞所產(chǎn)生的一種具有抗病毒、抗腫瘤和免疫調(diào)節(jié)等多種生物學(xué)活性的糖蛋白⑵typesandpropertiesbindstosurfacereceptorofneighboringcells⑶

Mechanismofantiviralactivitythesynthesis

ofantiviralprotein(AVP)

induceIFNbyblockingthetranslationofviralproteinsinhibitthereplicationofviruses

AVP:?

2’-5’Asynthetase(2’-5’A合成酶)?proteinkinaseR(蛋白激酶,PKR)?

phosphodiesterase(磷酸二脂酶)(degradeviralmRNA)(inhibittranslationofviralprotein)(inactivateinitiationfactorofprotein-synthesis)

⑷Featureofantiviralactivity

?inhibitreplicationofavarietyofviruses?onlyinhibitreplicationofvirus?species-specific

i.e.broadspectrum(廣譜)/non-specific

(notkilldirectlyvirus)thebody’sfirst-linedefenseagainstviralinfection⑸ActionofIFNinantitumorandimmunoregulation

Pathogen-associatedmolecularpatterns,PAMPPatternrecognitionreceptors,PRRToll-likereceptors,TLRPathogen-associatedmolecularpatternsCHALLENGE:Howcanthehostdiscriminatelargenumbersofdiversepathogensfromeachother&/orfromselfusingarestrictednumberofreceptors?SOLUTION:AllmulticellularorganismsareabletorecognizeandeliminatepathogensDespitetheirextremeheterogeneity,pathogenssharehighlyconservedmolecules,called“pathogen-associatedmolecularpatterns〞(PAMPs)2.Mechanismofspecificimmunity(對(duì)特異性抗原產(chǎn)生的應(yīng)答,并獲得特異免疫功能)(alsocalledadaptiveimmunity)

Mucosalimmunity

Humoralimmunity(HI)

Cell-mediatedimmunity(CMI)Mucosalimmunity?Unencapsulatedsubepitheliallymphoidfoundinthegastrointestinal,respiratoryandurogenitaltracts?Function*secreteSIgA*takepartinlocalimmuneresponseandsystemicimmuneresponse(i.e.localimmunity)(suchasGALT,BALT,tonsil)

physicalbarrierslikecastlewalls,fencesandpalisades.

Mucosalimmunesystemarenotonlyphysicalbarriersbutalsomightbethehuntinggroundsofprobioticorganisms.Skin,membranesandMISDC’sfunctioninmucosalimmunityImmatureDCdistributewidelyinmucousmembranePlayasabridgeconnectingthenon-specificimmuneresponseandspecificimmuneresponseInteractionbetweenCDandSIgATcelleffectorTcellCD4+Th1CD8+T(CTL)TmBcellplasmacellAb

BmHIAgCMI

Th2(CK)specificimmunity:specificandmemoryHumoralimmunity(HI)?effectormolecule?effectantibodyCell-mediatedimmunity(CMI)

orcellularimmunity?effectorcell

?effect*CD8+

CytotoxicTlymphocyte(CTL)*

CD4+Th1killtargetcelldirectly(feature,mechanism)

*secretecytokine(IL-2,IFN-,TNF-)*inducecellularimmunityandDTH

CTL:CD4+Th1:毒力毒素侵襲力外毒素內(nèi)毒素入侵門戶入侵?jǐn)?shù)量SectionII:Anti-bacteriaimmunity

I.pathogenesisofbacteria黏附與穿入：菌毛繁殖擴(kuò)散：侵襲性酶抗吞噬與殺傷：莢膜、胞壁等Mechanism1.Immunityofanti-extracellularbacterialinfection2.Immunityofanti-intracellularbacterialinfection

1.Immunityofanti-extracellularbacterialinfectionextracellularbacteria

↓exotoxin/↓endotoxin/↓invasiveenzymelocalpyrogenicinflammation

Barrierstructure

Phagocytosisofphagocyte

Effectofantibodyandcomplement

?preventadhesion

?opsonization?activatecomplement?nutralizeexotoxin

Cellularimmunity

(CD4+Th2→→cytokine)

Others:NKcell,lysozyme,defensin2.Immunityofanti-intracellularbacterialinfection

intracellularbacterial

↓(intracellularparasitism)↓byimmunopathologic↓injury

chronicinfection

Phagocytosisofphagocyte

Cellularimmunity

Mucosalimmunity?CD4+Th1→cytokine→DTH?CTLSIgA:interfereinadhesion

LastedtimeofimmunityNonspecificimmunitySpecificimmunityⅢ.AntiviralimmunityLastedtimeofimmunity

Systemicviralinfectionwithviremia

Viralinfectionwithsingleserotype

Viralinfectionofmuchvariableinantigenicity---transientimmunity---long-lastingimmunity---long-lastingimmunity1.Nonspecificimmunity

Barriers

Effectsofcells

Antiviralsubstancesinnormaltissuesandbodyfluid

(placentabarrier)(M,NK

cell)?virus-neutralizingantibodies

*neutralizeinfectivityofvirus*types(IgG/IgM/sIgA)andmechanism?hemagglutinationinhibitionAb

(inhibithemagglutination;IgG/IgM)?complementfixationAb

(opsonization)2.SpecificimmunityViralprotein

induceB---HIT---CMI(processingandpresenting)

Humo